ClinVar Miner

Submissions for variant NM_000020.2(ACVRL1):c.206G>T (p.Cys69Phe) (rs1318118188)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000640447 SCV000762038 pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2019-04-10 criteria provided, single submitter clinical testing This sequence change replaces cysteine with phenylalanine at codon 69 of the ACVRL1 protein (p.Cys69Phe). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with ACVRL1-related disease (PMID: 21158752, Invitae). ClinVar contains an entry for this variant (Variation ID: 533353). This variant affects a cysteine residue located within the ACVRL1 protein ectodomain. Cysteine residues in this domain of ACVRL1 are involved in the formation of disulfide bridges critical for protein structure and stability (PMID: 22028876, 22718755, 22799562). In addition, missense substitutions within the ACVRL1 ectodomain affecting cysteine residues are overrepresented in patients with HHT (PMID: 20501893, 26176610 and www.hhtmutation.org). A different missense substitution at this codon (p.Cys69Arg) has been reported in an individual affected with hereditary hemorrhagic teleangiectasia (PMID: 16525724). For these reasons, this variant has been classified as Pathogenic.

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